PROJECT SUMMARY/ABSTRACT We are the first group to demonstrate chronic vitamin B3 (niacin and niacinamide) deficiency in individuals with Parkinson's disease (PD). Niacin and niacinamide are the source of NAD which supplies energy and DNA repair to every cell in the body. PD patients frequently report symptoms which we believe are related to the vitamin deficiency, including daytime fatigue, sleep dysfunction and low-level mood. In addition, niacin but not niacinamide acts on GPR109A, an anti-inflammatory receptor. We are also the first group to show elevated GPR109A levels in the white blood cells (macrophages) and substantia nigra of PD patients, providing additional evidence of the consequences of chronic niacin deficiency in PD. In this exploratory trial, we propose to provide over-the-counter nutritional supplementation to test the hypothesis that correcting the deficiency via niacin's dual actions (energy supply and anti-inflammation) will improve symptom outcomes and reduce inflammation better than niacinamide. Aim 1. To determine whether niacin supplementation will reduce inflammation and improve the symptoms of PD patients better than niacinamide. Aim 2. To determine whether macrophage polarization and mitochondrial boost will reflect niacin and niacinamide supplementation independently. We will accomplish these aims with a two-arm double blind, randomized, fixed-dose, parallel niacinamide- controlled intention-to-treat 18-month pre-post prospective cohort design with mid-point assessment. The primary endpoint of this trial will be a decrease in the severity of motor symptoms as assessed by the Unified Parkinson's Disease Rating Scale Motor Section (UPDRS III). Secondary endpoints include wearable- technology measurements to document improvements in balance control and cognitive functions including nightsleep and executive control, as well as increased glycolysis and decreased GPR109A levels.